Endothelial progenitor cells in vascular regenerative medicine : towards 'designer blood vessels' and 'therapeutic neovascularization'

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The ability to restore vascular perfusion at sites of ischemic damage is essential for tissue regeneration. However, current therapies aimed to restore vascular perfusion are only successful when the large-diameter blood vessels (internal diameter (ID) > 6 mm) are affected. Hence, novel therapies such as tissue engineering of ‘designer’ blood vessels and (stem) cell therapy for therapeutic neovascularization are warranted. In this thesis we have investigated the cellular plasticity of endothelial progenitor cells (EPC) and explored its applicability for vascular regenerative medicine. In part I, we have found that human EPC contain the intrinsic capacity to differentiate into both mature and functional endothelial cells (EC) and smooth muscle cells (SMC) on degradable biomaterials. These EC and SMC can be employed to tissue engineer bioartificial autologous small-diameter blood vessels (figure 1A). Furthermore, in part II, we have identified a paracrine function of EPC during (therapeutic) neovascularization by the secretion of pro-angiogenic growth factors and cytokines (figure 1B).
Thus, the EPC offers enormous potential for tissue engineering of ‘designer’ blood vessels as well as in (stem) cell therapy. Hence, in future perspective, EPC-based therapies will enable true tissue regeneration therapies and pose great possibilities for autologous therapies. In this chapter we will discuss the cellular plasticity of EPC and how that can be used to alleviate the pitfalls of current (cardio)vascular therapies. Also, we discuss future challenges for vascular regenerative medicine that originate from this thesis.

	Title and contents
	Chapter 1
	Chapter 2
	Chapter 3
	Chapter 4
	Chapter 5
	Chapter 6
	Chapter 7
	Chapter 8
	Chapter 9
	Research summary
	An epiloque (general discussion)
	Nederlandse samenvatting
	Abbreviations
	References
	Curriculum vitae and publication list
	Dankwoord
	Complete thesis

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